Optically active carboxylic acids represented by the formula I: ##STR1## where R.sub.2 is alkyl, cycloalkyl, aralkyl or aryl, and n is 1 or 2, are useful, for example, as intermediates for the synthesis of various physiologically active materials. For example, the compound D(-)-3-mercapto-2-methylpropanoic acid having the formula: ##STR2## can serve as a key intermediate in the synthesis of 1-(2S)-3-mercapto-2-methylpropionyl]-L-proline (captopril), having the formula: ##STR3## and [1(R*),2.alpha.,4.alpha.]-1-[3-(benzoylthio)-2-methyl-1-oxopropyl]-4-(phen ylthio)-L-proline (zofenopril), having the formula: ##STR4## The beneficial activity of captopril and zofenopril depends on the configuration of the mercaptoalkanoyl moiety and the compounds of the S configuration are about 100 times more potent than the corresponding R-enantiomers. Thus, the S-enantiomers illustrated by formula I are much more desirable for such purposes than their R-enantiomer counterparts.
Prior art processes have utilized chemical and enzymatic resolution procedures. For example, carboxylic acids of the formula: ##STR5## where R.sub.1 is hydrogen or ##STR6## and R.sub.3 is alkyl, cycloalkyl, aralkyl or aryl, are prepared as racemic mixtures which can be separated into the R- and S-enantiomeric forms using chemical resolving agents. The so-provided S intermediates can then be used to prepare the desired products. Chemical resolution techniques have the distinct disadvantage, however, that large amounts of very expensive resolving agents are required. Additionally, the processes themselves are cumbersome and the yield is relatively low.
Alternatively, racemic compounds of the formula: ##STR7## can be directly coupled to X (which is L-proline in the case of captopril, and L-4-phenylthioproline in the case of zofenopril) to produce diastereomers of the general formula: ##STR8## The SS-diastereomer of these compounds can be isolated. Thereafter, the sulfhydryl or benzoylthio groups corresponding to captopril and zofenopril, respectively, can be provided to the left side of the molecule by known methods. However, a drawback to this process is that an equal amount of the RS-diastereomer is formed which must be discarded. This is highly undesirable in view of the cost of L-proline and derivatives thereof.
U.S. Pat. No. 4,629,701 provides resolved carboxylic acids by subjecting a compound containing both a carboxylic acid ester as well as a thioester group to an enzyme capable of asymmetrically hydrolyzing such a compound. It was found that while the carboxylic acid ester moiety is hydrolyzed to the acid form, the racemic compound is also resolved into the S or R configuration in improved yields and at lower costs than possible with chemical resolution techniques. Hydrolysis of the thioester group, as well as the carboxylic acid ester group is not, however, disclosed by this patent.